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National Institute of Environmental Health Sciences

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Publication Detail

Title: The Feverfew plant-derived compound, parthenolide enhances platelet production and attenuates platelet activation through NF-ýýB inhibition.

Authors: Sahler, Julie; Bernard, Jamie J; Spinelli, Sherry L; Blumberg, Neil; Phipps, Richard P

Published In Thromb Res, (2011 May)

Abstract: Few treatments are available that can safely and effectively stimulate new platelet production for thrombocytopenic patients. Additionally, recipients of transfused platelets may experience an inflammatory response due to stored platelets becoming unnecessarily activated, thus creating the need for suitable agents that will dampen undesirable platelet activation. We investigated the effect of the feverfew plant-derived compound, parthenolide on platelet production and platelet activation because of its well-studied ability to induce apoptosis or differentiation in some types of cancer.Parthenolide was used to treat human megakaryoblastic cell lines, primary human and mouse megakaryocytes. Resulting platelet production and function was measured via flow cytometry. The two most common parthenolide signaling mechanisms, oxidative stress and nuclear factor-ýýB inhibition, were assessed within the megakaryocytes using reactive oxygen species, glutathione and luciferase reporter assays. The influence of parthenolide on ex vivo platelet activation was tested with parthenolide pretreatment followed by collagen or thrombin activation. The resulting P-selectin surface expression and released soluble CD40 ligand was measured.Parthenolide stimulates functional platelet production from human megakaryocyte cell lines, and from primary mouse and human megakaryocytes in vitro. Parthenolide enhances platelet production via inhibition of nuclear factor-ýýB signaling in megakaryocytes and is independent of the parthenolide-induced oxidative stress response. Additionally, parthenolide treatment of human peripheral blood platelets attenuated activation of stimulated platelets.Overall, these data reveal that parthenolide has strong potential as a candidate to enhance platelet production and to dampen undesirable platelet activation.

PubMed ID: 21272923 Exiting the NIEHS site

MeSH Terms: Animals; Anti-Inflammatory Agents, Non-Steroidal/pharmacology; Blood Platelets/cytology; Blood Platelets/drug effects*; Blood Platelets/metabolism; Cell Line; Humans; Megakaryocyte Progenitor Cells/cytology; Megakaryocyte Progenitor Cells/drug effects; Megakaryocyte Progenitor Cells/metabolism; Mice; Mice, Inbred C57BL; NF-kappa B/antagonists & inhibitors*; NF-kappa B/metabolism; Platelet Activation/drug effects*; Sesquiterpenes/pharmacology*; Tanacetum parthenium/chemistry*

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